Table of Contents
1
UI - 11743581
AU - Yan H; Dobbie Z; Gruber SB; Markowitz S; Romans K; Giardiello FM;
TI -
Kinzler KW; Vogelstein B
Small changes in expression affect predisposition to tumorigenesis.
SO - Nat Genet 2002 Jan;30(1):25-6
AD - The Howard Hughes Medical Institute, The Oncology Center, and The
Department of Medicine, The Johns Hopkins Medical Institutions,
Baltimore, Maryland 21231, USA.
We have used quantitative measures of gene expression to show that
constitutional 50% decreases in expression of one adenomatous polyposis
coli tumor suppressor gene (APC) allele can lead to the development of
familial adenomatous polyposis.
2
UI - 11521793
AU - Olopade OI; Pichert G
TI -
Cancer genetics in oncology practice.
SO - Ann Oncol 2001 Jul;12(7):895-908
AD - University of Chicago Pritzker School of Medicine, Illinois, USA.
folopade@medicine.bsd.uchicago.edu
Cancer is a genetic disease caused by the progressive accumulation of
mutations in critical genes that control cell growth and
differentiation. Completion of the Human Genome Project promises to
revolutionize the practice of Medicine, especially Oncology care. The
tremendous gains in the knowledge of the structure and function of human
genes will surely impact the diagnosis, prognosis and treatment of
cancer. Moreover, it will lead to more effective cancer control through
the use of genetics to quantify individual cancer risks. This article
reviews the current status of genetic testing and counseling for cancer
risk assessment and will suggest a framework for integrating such
counseling into oncology practice.
3
UI - 11808944
AU - Matsumoto T; Lida M; Kobori Y; Mizuno M; Nakamura S; Hizawa K; Yao T
TI -
Genetic predisposition to clinical manifestations in familial
adenomatous polyposis with special reference to duodenal lesions.
SO - Am J Gastroenterol 2002 Jan;97(1):180-5
AD - Department of Endoscopic Diagnostics and Therapeutics, Kyushu University
Hospital, Fukuoka, Japan.
OBJECTIVES: In familial adenomatous polyposis (FAP), genetic
predisposition for duodenal adenomatosis has not been investigated
precisely. The aim of this study was to investigate the correlation
between adenomatous polyposis coli (APC) gene mutation and duodenal
adenomatosis in FAP. METHODS: APC gene mutation was determined by means
of a protein truncation test in 34 patients from 25 families with FAP.
The prevalence and grade of duodenal adenomatosis were compared among
the proximal mutation group (exons 1-9), the distal mutation group
(exons 10-15), and the undetermined groups. The correlation between the
course of duodenal adenomatosis and APC gene mutation was
retrospectively investigated in 19 patients. RESULTS: The prevalence of
duodenal adenomatosis was lower in the proximal mutation group (44%)
than in the distal mutation (100%) and undetermined (83%) groups. In
patients with positive duodenal adenomatosis, the endoscopic grade did
not differ among the groups. The endoscopic grade increased in two of
the four patients with the proximal mutation group (50%), in three of 10
patients with the distal mutation group (30%), and in two of five
patients (40%) with the undetermined group. CONCLUSIONS: Truncating APC
gene mutation proximal to exon 9 may contribute to the less frequent
development of duodenal adenomatosis in FAP, but severity and
progression of duodenal adenomatosis do not seem to be determined by APC
gene mutation alone.
4
UI - 11771446
AU - Metzger U; Schnider A
TI -
Prophylactic surgery in families with familial adenomatous polyposis
(FAP) and in colitis.
SO - Swiss Surg 2001;7(6):278-80
AD - Department of Surgery, City-Hospital Triemli, Zurich.
Colorectal cancer is the second most common cause of death from
malignant tumors in western countries with approximately 3800 new
cases/year in Switzerland. For individuals known to be at high risk for
the development of colorectal cancer, screening, chemoprevention and/or
prophylactic surgery are the only tools to avoid unnecessary premature
death from this disease. With modern molecular and/or genetic testing
the risk of developing colorectal cancer can be more precisely estimated
on an individualized basis. These individuals need to be enrolled in
strong surveillance programs and are clear candidates for prophylactic
surgery. The risk of prophylactic surgery (morbidity, mortality, quality
of life following surgery) must be clearly weighted against the
increasing risk of cancer. These patients should be treated in
experienced centers for colorectal surgery in close connection with a
genetic testing and counseling team, a molecular laboratory and a
psychological support group.
5
UI - 11754114
AU - Davidson S; Leshanski L; Rennert G; Eidelman S; Amikam D
TI -
Maternal mosaicism for a second mutational event--a novel deletion--in a
familial adenomatous polyposis family harboring a new germ-line mutation
in the alternatively spliced-exon 9 region of APC.
SO - Hum Mutat 2002 Jan;19(1):83-4
AD - Molecular Oncology Laboratory, Rambam Medical Center, Haifa, Israel.
Familial Adenomatous Polyposis (FAP) is an autosomal dominant heritable
disorder caused by germ-line mutations in the APC gene. To date, more
than 300 germ-line mutations within this gene have been described. Using
PCR, SSCP and DNA sequencing, we have identified a new mutation in the
alternatively spliced region of exon 9 (1042C-->T), which results in a
stop signal. This mutation manifested an aggressive form of FAP with
onset of symptoms in one proband at age 17. Our results differ from
reported exon 9 mutations in the spliced-out portion of the gene
manifesting an attentuated form of FAP (AAPC) [Varesco et al 1994; van
der Luijt et al. 1995; Curia et al. 1998; Young et al. 1998]. When
analyzing this family, we encountered a mutant FAP gene which had
undergone a second mutational event, a deletion. In addition to linkage
analysis, both the occurrence of the two exon 9 mutation-carrier
siblings, of which one is affected, harboring the same novel deletion in
one generation of this family, and its absence in both parents indicates
the existence of maternal germ-line mosaicism for cells bearing the
latter second mutational event. Our study is only the second report of
parental mosaicism in the APC gene. Copyright 2001 Wiley-Liss, Inc.
6
UI - 11831075
AU - Kronborg O
TI -
[Colorectal cancer screening]
SO - Ugeskr Laeger 2002 Jan 7;164(2):153-5
AD - Kirurgisk afdeling A, Odense Universitetshospital, DK-5000 Odense C.
7
UI - 11779834
AU - Silverman KA; Koratkar R; Siracusa LD; Buchberg AM
TI -
Identification of the modifier of Min 2 (Mom2) locus, a new mutation
that influences Apc-induced intestinal neoplasia.
SO - Genome Res 2002 Jan;12(1):88-97
AD - Kimmel Cancer Center, Jefferson Medical College, Philadelphia,
Pennsylvania 19107-5541, USA.
Min (Multiple intestinal neoplasia) mice carry a dominant mutation in
the adenomatous polyposis coli (Apc) gene and develop multiple adenomas
throughout their intestinal tract (Moser et al. 1990; Su et al 1992).
Polyp multiplicity in Min mice is greatly influenced by genetic
background. A modifier locus, Mom1 (Modifier of Min 1), was identified
and localized to distal mouse chromosome 4 (Moser et al. 1992; Dietrich
et al. 1993), and accounts for some of the genetic variance in polyp
multiplicity. Mom1 is a semidominant modifier of polyp size and
multiplicity in Min mice (Gould and Dove 1997), and encodes the
secretory type II nonpancreatic phospholipase A2 (Pla2g2a) gene (MacPhee
et al. 1995; Cornier et al. 1997, 2000). We now report the
identification of a second Modifier of Min 2 (Mom2) locus that is the
result of a spontaneous mutation. One resistant Mom2 allele can suppress
88%-95% of polyps detected in Apc(Min)/+ mice, indicating that Mom2 acts
in a dominant fashion. Linkage analysis has localized Mom2 to distal
mouse chromosome 18. The effects of the Mom2 locus on reducing polyp
multiplicity are stronger than the effects of the Mom1 locus, in both
the small and large intestines. Some Apc(Min)/+ mice that carried one
resistant Mom2 allele were tumor-free at 21 weeks of age, even in the
absence of a resistant Mom1 allele. Thus, the resistant Mom2 allele can,
in some cases, completely suppress the penetrance of the Apc(Min)
mutation.
8
UI - 11809680
AU - Cheadle JP; Krawczak M; Thomas MW; Hodges AK; Al-Tassan N; Fleming N;
TI -
Sampson JR
Different combinations of biallelic APC mutation confer different growth
advantages in colorectal tumours.
SO - Cancer Res 2002 Jan 15;62(2):363-6
AD - Institute of Medical Genetics, University of Wales College of Medicine,
Heath Park, Cardiff CF14 4XN, United Kingdom.
New facets to Knudsen's "two-hit" hypothesis have been proposed recently
in relation to adenomatous polyposis coli (APC): protein inactivation
may be selected weakly, and the two hits may be interdependent. We
reviewed published data on 165 sporadic and 102 familial adenomatous
polyposis-associated colorectal tumors with two characterized mutations.
Using a Poisson model, we redefined the mutation cluster region (MCR) to
residues 1281-1556 and confirmed that the locations of pairs of APC
mutations are interdependent (P < 0.0001). A mathematical model, based
on the data for sporadic tumors, implied different growth advantages for
different combinations of APC mutations: genotype I/I (I: mutation
inside MCR) was 3.9 times more likely to be selected than IO or IL (O:
mutation outside MCR, L: allelic loss), which were 27.8 times more
likely to be selected than OO or OL.
9
UI - 10634400
AU - Cetta F; Montalto G; Gori M; Curia MC; Cama A; Olschwang S
TI -
Germline mutations of the APC gene in patients with familial adenomatous
polyposis-associated thyroid carcinoma: results from a European
cooperative study.
SO - J Clin Endocrinol Metab 2000 Jan;85(1):286-92
AD - Interuniversity Center for Research in Hepatobiliary Disease, Institute
of Surgical Clinics, University of Siena, Italy.
Papillary thyroid carcinoma (PTC) is one extracolonic manifestation
affecting about 1-2% of patients with familial adenomatous polyposis
(FAP). Ninety-seven patients with FAP-associated PTC have previously
been reported, including 6 pairs of siblings. During a European
collaborative study, 15 patients with FAP-associated PTC were collected.
All 15 patients were females. The mean age at thyroidectomy was 24.9 yr
(range, 19-39 yr). In 13 subjects, APC germline mutations had been
detected; they were at codons 140, 593, 778, 976, 993, 1061 (n = 5),
1105 (n = 1), and 1309 (n = 2), respectively. A review of the literature
added 11 other patients with FAP-associated PTC and detection of
germline APC mutations; they were at codons 313 (n = 2), 698 (n = 3),
848 (n = 2), 1209 (n = 2), 1061 (n = 1), and 1105 (n = 1), respectively.
The latter led to formation of the same stop codon (TAA) at 1125-1126 as
the mutation at codon 1061. Therefore, 21 of 24 mutations were in exon
15 in the genomic area usually associated with congenital hypertrophy of
the retinal pigment epithelium (CHRPE), i.e. codons 463-1387. Typical
CHRPE was found in 17 of 18 affected patients who had specific
screening. Interestingly, 22 of the 24 patients had their mutation out
of the mutation cluster region (codons 1286-1513), which is currently
considered the hot spot mutation area, in particular for extracolonic
manifestations of FAP. The difference in the incidence of germline
mutations before and after codon 1220 between PTC and non-PTC FAP
patients was statistically significant (P<0.05) for both patients and
kindreds (P = 0.005 and P = 0.049, respectively). Even if most mutations
were scattered throughout the entire 5'-portion of exon 15, 8 of 23
patients (6 with mutation at 1061 and 2 with mutation at 1105; i.e. more
than one third) had the same truncated protein product. The awareness
that patients with PTC usually have APC mutations that cluster in a well
defined genomic area, in addition to giving a deeper insight into gene
function, could facilitate both earlier diagnosis and better treatment.
In particular, intensive screening for thyroid nodules after age 15 yr
is recommended when a single patient or an entire kindred have CHRPE
and/or mutations in the 5'-portion of exon 15.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
About OncoLink Contact OncoLink Privacy statement Disclaimer Link to OncoLink Home